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Mutations and epigenetic inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma (ccRCC) that may originate from chronic inflammation. However, the role of VHL loss of function in the development of ccRCC via inflammation remains poorly understood. VHL-mutant cells exhibit metabolic abnormalities that can cause chronic endoplasmic reticulum (ER) stress and unfolded protein response. We hypothesize that unresolved ER stress induces the inflammatory responses observed in ccRCC. ER stress markers including BiP and XBP1s were significantly increased in cultured and primary VHL loss-of-function kidney cells. In epithelial cells, the kinase activity of IRE1a was required for the induction of NF-κB and JNK and for the recruitment of macrophages. IRE1a kinase activity was also important for the development of fibrotic phenotype in conditional Vhlh knockout mice. Our results offer insights into the therapeutic potential against ccRCC development by relieving metabolic stress. Such cancer prevention strategy may be critical for high-risk cohorts such as the familial VHL disease patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the effects of HBx on the inhibition of tumorigenesis in nude mice injected with CCL13-HBx cells. Therefore, the characteristics of the induced tumors and the phenomenon of apoptosis were assessed. Methods: The induced tumors were identified using the specific marker of hepatocellular carcinoma (HCC), anti-α-fetoprotein (AFP), and their characteristics were pathologically examined. Apoptosis was detected by DNA fragmentation, and the expression of the proapoptotic proteins p53, Bax, Bad, caspase-3, and caspase-8 and the anti-apoptotic protein Bcl-2 was detected by Western blotting. To identify possible molecules involved in the inhibition of tumorigenesis, extracts of the induced tumors were separated by 2D-PAGE, and the proteins were identified by MS. Results: The tumors of the nude mice injected with CCL13 and CCL13-HBx cells were identified as HCCs. Moreover, HBx was found to suppress tumor growth via apoptosis in the nude mice injected with CCL13-HBx cells. The MS findings revealed that phosphorylated myosin light chain was a candidate molecule involved in the inhibition of tumorigenesis. Conclusion: HBx suppressed tumorigenesis in the nude mice injected with CCL13-HBx cells, which proved to be a good animal model for the in vivo study of the effects of HBx on tumorigenesis. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The hepatitis B virus X protein (HBx) plays critical roles in cell survival via modulation of signaling pathways. In our previous studies, we reported that HBx inhibited the growth of CCL13-HBx-stable cells (Chang-HBx cells) in vitro and tumor formation in vivo in CCL13-HBx-cell-injected nude mice; however, this inhibition mechanism is unclear. Methods: To investigate the role of HBx in Wnt-3/β-catenin signaling pathways, we focused on the key molecules GSK-3β and β-catenin, and analyzed by Western blotting and immunofluorescence staining. Results: Results indicated that following HBx induction, GSK-3β activity was up-regulated, the expression and accumulation of β-catenin in the nucleus were decreased, and cell proliferation was suppressed. Inhibition of GSK-3β activity by pharmacological inhibitors rescued the expression and accumulation of β-catenin in the nucleus and facilitated cell proliferation and growth following HBx induction. The localization of β-catenin, which is involved in cell proliferation, and mediated by GSK-3β activation was also demonstrated. Conclusion: Our findings suggest that HBx negatively regulated proliferation of CCL13-HBx-stable cells via the GSK-3β/β-catenin cascade. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The known function of hepatitis B virus X protein (HBx) is to determine the fate of cells by modulating various signaling pathways. In our previous study, we demonstrated that HBx inhibits tumor formation in nude mice injected with CCL13-HBx stable cell lines; however, the mechanism underlying this inhibition is unclear. Methods: To investigate the possible mechanisms underlying HBx involvement in CCL13-HBx cells, gene profiles were initially analyzed by DNA microarray technology and subsequently confirmed by performing semiquantitative RT-PCR and Western blotting. Furthermore, the phenomenon of cell death via apoptosis was detected via DNA fragmentation, TUNEL staining, caspase-3 activity assay, and propidium iodide (PI) staining. Results: The results indicated that HBx induction downregulated Wnt-3 and β-catenin that are involved in cell proliferation. Moreover, HBx induction repressed cell growth and downregulated the expressions of cyclin D1, CDK4, cyclin E, CDK2, and cyclin B1. Furthermore, HBx induction triggered cell death via apoptosis, as determined by DNA fragmentation, TUNEL staining, caspase-3 activity assay, and PI staining. Conclusion: Most importantly, our results indicated that HBx induction in the CCL13-HBx stable cell line downregulated Wnt-3/β-catenin expression and suppressed cell growth by repressing cell proliferation or triggering cell apoptosis. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Exercise-induced muscle damage can be caused by excessive or unfamiliar eccentric exercises. Hypoxia induces oxidative stress in C2C12 myoblasts, mimicking intracellular muscle injury. Under hypoxic conditions, the accumulation of reactive oxygen species causes cell death through apoptosis and ferroptosis. Identifying candidate natural products involved in oxidative stress and developing strategies to mitigate these effects have garnered significant attention. In the present study, we used Danshensu as a candidate product to determine its protective effects against hypoxia-induced C2C12 cell damage via apoptosis and ferroptosis. The results showed that Danshensu restored cell death and apoptosis by regulating B-cell lymphoma 2 protein, its associated X Protein and cleaved-caspase 3. Additionally, Danshensu restored ferroptosis by regulating glutathione peroxidase 4 and solute carrier family 7 member 11 protein under hypoxic conditions. Moreover, the accumulation of reactive oxygen species caused by hypoxia was attenuated in the presence of Danshensu. These findings provide new insights into the potential of Danshensu as an alternative treatment for hypoxia-induced damage to the skeletal muscle C2C12 cell line. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is characterized by persistent abnormalities in urinary function, structural abnormalities, or impaired excretory functions that indicate the loss of functional nephrons. Cardiovascular disease and death are the most common complications of chronic kidney disease. Once chronic kidney disease is established, treatment has proven ineffective. Therefore, research efforts should be devoted to uncovering early disease mechanisms and alternative treatment options. Traditionally, garlic has been used as a pharmacological agent, especially when aged, in addition to its application as a food flavoring agent. Studies have suggested that garlic has anti-inflammatory and immunomodulatory properties. The effects of garlic on renal function have been summarized in cell culture, animal, and clinical studies. [ABSTRACT FROM AUTHOR]

Iron plays a key role in the regulation of hepatic stellate cell activation during the pathogenesis of liver fibrosis. Prevention of hepatic stellate cell activation and promotion by activating hepatic stellate cells to death is a good strategy for resolution of liver fibrosis. Ferroptosis is an iron dependent cell death, which is characterized by accumulation of lipid peroxides. We have shown in our earlier studies that chrysophanol (isolated from Rheum palmatum rhizomes) promotes (hepatitis B virus X protein)-activated hepatic stellate cells to ferroptosis; however, the effect of desferal in our cell model is still unclear. In this study, we have shown that desferal reversed chrysophanol-induced lipid reactive oxygen species overproduction and cell death in (hepatitis B virus X protein)-activated T6 cells. Furthermore, desferal also alleviated and chrysophanol downregulated the expressions of α-smooth muscle actin, connective tissue growth fac, glutathione peroxidase 4, and solute carrier family 7-member 11 protein in hepatitis B virus X protein-activated T6 cells. In conclusion, desferal regulates ferroptosis induced by chrysophanol in hepatitis B virus X protein-activated hepatic stellate cell activation and fibrosis. [ABSTRACT FROM AUTHOR]

Supplementation with select nutrients facilitate wound healing, thereby supporting the association between nutrition and wound healing. In recent years, studies have assessed the relationship of amino acid supplements and basic nutrition with wound healing. The present study is a case report on about a 35-year-old woman whose wound measured 0.7 × 1 cm2 after laparoscopic surgery but did not heal for more than 5 weeks after surgery and drainage tube removal. Nutritional care comprising the required calories and a high-protein diet was initiated. The average actual daily calorie intake was 1,556 kcal (88% of the required amount), and the average daily protein intake was 91 g (126% of the required amount). After 11 days on a diet containing mixed amino acids (arginine, glutamine, and beta-hydroxy-beta-methylbutyrate), the wound size reduced from 0.7 × 1 cm2 to 0.3 × 0.5 cm2. The case findings suggest that the provision of sufficient calories and protein nutrition, supplemented with mixed amino acids containing arginine, glutamine, and beta-hydroxy-beta-methylbutyrate can contribute to the healing of chronic wounds. [ABSTRACT FROM AUTHOR]

A health belief model is used to evaluate people's beliefs about health problems and predict engagement in health-promoting behaviors. Overweight and obesity are health problems that could be corrected by healthier diet. Eighty-seven employees of the Taipei Tzu Chi Hospital participated in a month-long program that offered 500-calorie vegetarian meals. The health belief model questionnaire was designed and administered. Body composition (weight, body mass index, body fat, body water, and muscle mass) was measured weekly. Additionally, the number of meals taken and visits to nutrition consultants were analyzed. Overall, a higher perceived susceptibility was related to a decrease in weight, body fat, and muscle. Higher perceived benefits or higher perceived barriers were both related to a decrease in weight and body fat, but to an increase in body water and muscle. In the overweight or obese group, a significant correlation was found between perceived barriers and weight. No significant relationship was found between the health belief model and the total number of meals or number of visits to nutrition consultants. Perceived benefits and barriers were significantly related to changes in weight, body fat, body water, and muscle. With vegetarian meal plans as the cue for action, the health belief model can be utilized to predict changes in body composition. [ABSTRACT FROM AUTHOR]

Oral cancer is a type of head and neck cancer that can be life threatening. Unfolded protein response and endoplasmic reticulum stress play a critical role in carcinogenesis. However, prolonged activation of unfolded protein response also activates apoptosis. Thus, a new treatment strategy maybe activation of extensive unfolded protein response and severe endoplasmic reticulum stress in tumor cells. We examined the pharmacological effects of chrysophanol on an oral cancer cell line FaDu, a hypopharyngeal squamous cell carcinoma specifically for its ability to cause cell death via unfolded protein response and endoplasmic reticulum stress. We measured the expression of binding immunoglobulin protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1a, and activating transcription factor 6 after treatment with chrysophanol in absence or presence of APY29 (an inhibitor of phosphorylated inositol-requiring enzyme-1a). Chrysophanol caused cell death via upregulations of binding immunoglobulin protein that is also known as 78-kDa glucose-regulated protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1a, and activating transcription factor 6. This activity was reversed by APY29. Thus, chrysophanol could be a useful antitumor agent for the management of oral cancer. [ABSTRACT FROM AUTHOR]

Oral cancer is a type of head and neck cancer that can be life threatening if not diagnosed and treated early. Ferroptosis is a type of programmed or regulated cell death dependent on iron and reactive oxygen species but is a caspase-independent form of non-apoptotic cell death. Therefore, there is a need to identify candidate natural compound that may attenuate carcinogenesis through ferroptosis. To this end, we determined the pharmacological effects of chrysophanol on ferroptosis in two different oral cancer cell lines--FaDu, a hypopharyngeal squamous cell carcinoma and SAS, a poorly differentiated squamous cell carcinoma cell line from human tongue primary lesion. Results indicated that chrysophanol caused overproduction of lipid reactive oxygen species, decreased the level of glutathione peroxidase 4, and increased the level of lipocalin-2 and CCAAT-enhancer-binding protein homologous protein. These findings suggest that chrysophanol has the therapeutic potential to alleviate the progression of oral carcinogenesis through activation of ferroptosis. [ABSTRACT FROM AUTHOR]

Danshensu, isolated from Salvia miltiorrhiza (Danshen), is known to have anti-inflammatory properties. Therefore danshen is extensively used in many nutraceutical formulations. Reactive oxygen species are essential for the development of hypoxia-induced inflammation. Generation of reactive oxygen species by infiltrating macrophages is common in various diseases such as cardiovascular disease, neurodegenerative disease, tumor, and aging. To explore the mechanism underlying the attenuation of inflammation, we used RAW 264.7 cells as a model and hypoxia as an inducer of inflammation. The results showed the protective mechanism of danshensu on reactive oxygen species production, hypoxia-inducible factor 1-alpha expression, c-Jun N-terminal kinase phosphorylation, nuclear translocation of nuclear factor kappa B, and inducible nitric oxide synthase expression following hypoxia in RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

In this short letter to the editor, we have introduced and summarized the role of anti-angiogenesis, microRNA, and exosomes in cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apop- totic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2',7'-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR. [ABSTRACT FROM AUTHOR]

6-MSITC (Methylsulfinyl hexyl isothiocyanate) is a bioactive compound found in wasabi that contains anti-inflammatory, anti-carcinogenic, and antioxidative properties. In this article, we summarize and discuss the current studies on the role of 6-MSITC on inflammatory diseases and carcinogenesis. [ABSTRACT FROM AUTHOR]

Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1-induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1. [ABSTRACT FROM AUTHOR]